Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Studies have shown that persons with type 1 diabetes can significantly reduce the risk of complications associated with the disease by actively monitoring their blood glucose levels (The Diabetes Control and Complications Trial Research Group (1993) New Eng. J. Med., 329:977-986). However, the current method of monitoring blood glucose levels involves painful finger sticks. Many diabetic patients fail to actively manage their glucose for the primary reasons of finger soreness, pain, inconvenience, and fear of needles (Burge, M. R. (2001) Diabetes Care, 24:1502-1503).
Researchers have been searching for ways to noninvasively measure blood glucose in diabetic subjects for years (Sieg et al. (2005) Diabetes Tech. Therap. 7:174-97; Zheng et al. (2000) Diabetes Tech. Therap. 2:17-25). This research has taken one of two approaches: using infrared or near infrared technology to noninvasively obtain optical signatures that are known to correlate with glucose levels; or taking samples of interstitial fluid for analysis. Both of these approaches pose problems, including accuracy issues, skin irritation, and calibration problems (Sieg et al. (2005) Diabetes Tech. Therap. 7:174-97; Zheng et al. (2000) Diabetes Tech. Therap. 2:17-25).
The normal cochlea does not just receive sound. The cochlea also produces low-intensity sounds called otoacoustic emissions (OAEs) that can be evoked using audio stimuli (Brownell, W. E. (1990) Ear and Hearing, 2:82-92). OAEs can provide a noninvasive test of the cochlear mechanical response to acoustic stimuli. OAE tests are already widely used in humans and animals to study cochlear function and the efferent system (Berlin et al. (2002) “Hair Cell Micromechanics and Otoacoustic Emissions” Delmar Learning, Thomason Learning, Inc, Clifton Park, N.Y.).
Suckfull et al. (Acta Oto-Lanryngologica (1999) 119: 316-21) found that OAE amplitudes decreased with an influx of glucose in rabbits under unmasked conditions. Using single-frequency tone bursts to evoke OAEs, Suckfull et al. recorded OAE amplitudes in rabbits while infusing their blood serum with 40% glucose at 10 ml/kg/h and observed a decrease in the evoked OAE amplitudes in response to the elevated glucose level. In contrast, Sasso et al. (Metabolism (1999) 48:1346-1350) examined OAE amplitudes during hyperglycemia for 10 diabetic and 10 nondiabetic human subjects and found no correlation with glucose levels. Notably, the Sasso et al. experiments used clicks to evoke OAEs while Suckfull et al. used pure-tones to evoke them. A click is essentially a representation of all frequencies within the audio spectrum. Neither Sasso et al. nor Suckfull et al. determined a specific correlation between OAE and analyte or glucose concentration or examined the effects of glucose or an analyte on an OAE measured during contralateral or ipsilateral masking.